Semyanov Alexey, Walker Matthew C, Kullmann Dimitri M, Silver R Angus
Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
Trends Neurosci. 2004 May;27(5):262-9. doi: 10.1016/j.tins.2004.03.005.
GABAA receptors not only respond to the local release of GABA from presynaptic terminals, but can also mediate a persistent 'tonic current'. This reflects the activation of high-affinity GABAA receptors by ambient GABA concentrations. Tonic GABAA-receptor-mediated signalling occurs in different brain regions, shows cell-type-specific differences in magnitude and pharmacology, and changes during brain development. Some clues to the adaptive significance of this phenomenon are beginning to emerge: in cerebellar granule cells, it alters the gain of transmission of rate-coded sensory information; in the hippocampus, it acts in a cell-type-specific manner to regulate the excitability of the network. Because tonic conductances can be modulated by changes in GABA release and uptake, and by modulators of high-affinity GABAA receptors including neurosteroids, this phenomenon provides a potentially important new window onto neuronal information processing and pathological states such as epilepsy.
γ-氨基丁酸A型(GABAA)受体不仅对来自突触前终末的γ-氨基丁酸(GABA)的局部释放作出反应,还能介导持续的“紧张性电流”。这反映了环境中GABA浓度对高亲和力GABAA受体的激活作用。紧张性GABAA受体介导的信号传导发生在不同的脑区,在大小和药理学方面表现出细胞类型特异性差异,并且在脑发育过程中会发生变化。关于这一现象的适应性意义的一些线索开始显现出来:在小脑颗粒细胞中,它改变了速率编码感觉信息传递的增益;在海马体中,它以细胞类型特异性的方式调节网络的兴奋性。由于紧张性电导可通过GABA释放和摄取的变化以及包括神经甾体在内的高亲和力GABAA受体调节剂进行调节,这一现象为神经元信息处理和癫痫等病理状态提供了一个潜在的重要新窗口。